NX-1207 is an investigational drug for the treatment of BPH that is currently in phase III double-blinded, placebo-controlled, multicenter clinical trials in the USA. It is a new therapeutic protein of proprietary composition with selective pro-apoptotic properties [Nymox Pharmaceutical Corporation, data on file; Shore et al. 2008, 2007; Cowan et al. 2008, 2007; ClinicalTrials.gov]. Apoptosis is programmed cell death and is a natural mechanism in the body for cell suicide. NX-1207-treated cells in vivo and in vitro show strong positivity for standard apoptotic cell-death markers, such as caspases and Annexin V (Figure 1). The drug is sterile formulated in phosphate buffered saline (PBS) at physiologic pH (7.4) and is administered through TRUS guidance by injection directly into the periurethral transitional zone of the prostate. The transitional zone of the prostate surrounds the urethra; the enlargement of the transitional zone is believed to play a significant role in BPH and the association of symptoms with LUTS. NX-1207 has been demonstrated to induce focal cell loss in prostate tissue through apoptosis, leading to prostate tissue shrinkage with resultant short- and long-term symptomatic improvement. In the current ongoing phase III clinical trials of NX-1207 for BPH, NX-1207 is administered to patients with moderate-to-severe BPH (AUASI ≥ 15), and with prostate volumes between 30 ml and 70 ml (Table 1).
Cell culture photomicrograph illustrating NX-1207-induced apoptotic cell death, strong diffuse Annexin V positivity and diffuse loss of membrane integrity. Scale bar = 10 µm. (Nymox Pharmaceutical Corporation, Hasbrouck Heights, NJ, USA).
Inclusion and exclusion criteria for phase III studies NX02-0017 and NX02-0018.
Mode of administration
NX-1207 has been administered as an office-based procedure by a urologist. Patients receive antibiotic prophylaxis for 3 days before the procedure and for 1 week after. NX-1207 0.25 mg/ml is administered by transrectal intraprostatic injection with ultrasound guidance (Figure 2) using a no. 22 gauge needle. A total of 5 ml is injected into each lobe of the transition zone of the prostate. The procedure is of brief duration (5–10 min in total) and does not require local anesthesia, intravenous sedation, or urethral catheterization. Patients have reported minimal discomfort from the injection procedure itself. No specialized training for the urologist is required, assuming familiarity with other TRUS-guided procedures such as TRUS-guided prostate biopsy.
Ultrasound image showing NX-1207 injection (arrow on left) in a subject with benign prostatic hyperplasia. (Nymox Pharmaceutical Corporation, Hasbrouck Heights, NJ, USA).
Completed phase II studies
Two completed US phase II trials provided positive evidence of the safety and efficacy of NX-1207 for the treatment of BPH, confirming the results from two earlier US phase I/II studies [Nymox Pharmaceutical Corporation, data on file; Shore et al. 2007, 2008; Cowan et al. 2007]. The first phase II trial (0014) was a multicenter, randomized, double-blind, placebo-controlled study involving 43 clinical trial sites in the USA. A total of 175 men with BPH were enrolled in the study and randomized to receive a single TRUS-guided intraprostatic injection of one of three doses of NX-1207 (2.5, 5.0, or 10 mg), or a saline vehicle placebo control. The primary endpoint was improvement in AUASI score after 90 days. All three doses of NX-1207 showed therapeutic effect at the study’s primary endpoint (90 days after treatment) with the mean improvement in AUASI score ranging from 11.0 (2.5 mg; p = 0.008 when compared with placebo) to 8.7 (5.0 mg; p = 0.08) to 8.1 (10 mg; p = 0.17) with a total pooled improvement of 9.35 (p = 0.017). Subjects receiving NX-1207 had mean prostate glandular volume (PGV) reduction of 6.8 ml in the transition zone (p
By and large drugs for BPH long term have an improvement only of 5-6 on the AUS score. By the way NYMOX drug improvement of 10 is not sustained; after some time it drops to 7-8 but is maintained over several months.
Approximately half the patients who take drugs find them non effective and this is where NYMOX will be positioned by physicians. They will try the medications and if they don't work the NYMOX injection before considering surgery. Recordati their partner in Europe is on record (pun intended) they intend to position NYMOX in this niche in their trial.
Every year 4-8 Billion is spent in the US on BPH; if NYMOX can get a fraction of that; they will do well.
I tried back in 2004 to get in the NX-1207 trial. Went through the local urologist before I drove all the way to Birmingham, AL but was rejected because I wasn't severe enough; was what the Nymox folks told me. Now I'm 59 years old, with extreme BPH and none of the present medicines work for me at all.
When will NX-1207, which shows both positive results for both prostate cancer and BPH be available for all of us suffering from this disease? I'm sure it's the Flomax/Proscar companies blocking the success of Nymox but wish the FDA would approve this!!!